This invention relates to imidazopyridine compounds that have ether or thioether substitution at the 1-position, and that may contain additional functionality. The invention also provides pharmaceutical compositions containing these compounds and methods of inducing cytokine biosynthesis by administration of the compounds.
The first reliable report on the 1H-imidazo[4,5-c]quinoline ring system, Backman et al., J. Org. Chem. 15, 1278-1284 (1950) describes the synthesis of 1-(6-methoxy-8-quinolinyl)-2-methyl-1H-imidazo[4,5-c]quinoline for possible use as an antimalarial agent. Subsequently, syntheses of various substituted 1H-imidazo[4,5-c] quinolines were reported. For example, Jain et al., J. Med. Chem. 11, pp. 87-92 (1968), synthesized the compound 1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline as a possible anticonvulsant and cardiovascular agent. Also, Baranov et al., Chem. Abs. 85, 94362 (1976), have reported several 2-oxoimidazo[4,5-c]quinolines, and Berenyi et al., J. Heterocyclic Chem. 18, 1537-1540 (1981), have reported certain 2-oxoimidazo[4,5-c]quinolines.
Certain 1H-imidazo[4,5-c]quinolin-4-amines and 1- and 2-substituted derivatives thereof were later found to be useful as antiviral agents, bronchodilators and immunomodulators. These are described in, inter alia, U.S. Pat. Nos. 4,689,338; 4,698,348; 4,929,624; 5,037,986; 5,268,376; 5,346,905; and 5,389,640, all of which are incorporated herein by reference.
Substituted 1H-imidazopyridine-4-amine compounds useful as immune response modifiers are described in U.S. Pat. Nos. 5,446,153; 5,494,916; 5,644,063; 6,525,064; 6,545,016; and 6,545,017. The compounds described in these patents do not have ether substitution at the 1-position. Certain 1H-imidazo[4,5-c]quinolin-4-amines that have amide, sulfonamide, and urea functionality at the 1-position are described in U.S. Pat. Nos. 6,331,539; 6451,810; and 6,541,485.
Despite these recent discoveries of compounds that are useful as immune response modifiers, there is a continuing need for compounds that have the ability to modulate the immune response, by induction of cytokine biosynthesis or other mechanisms.
In one aspect, the invention provides imidazopyridine compounds that have ether substitution at the 1-position. These compounds have the general formula (Ia): 
wherein X, W, and the various R variables are as defined herein. In other aspects, the invention provides pharmaceutical compositions containing the compounds and methods of using the compounds to achieve a therapeutic effect. Such effects include the induction of cytokine biosynthesis, the induction of interferon biosynthesis, treatment of viral conditions and treatment of neoplastic conditions. In other aspects, the invention additionally provides methods of making the compounds and intermediate compounds useful in their synthesis.
Many of the compounds of the invention have an ether linkage at the 1-position of the compounds. The compounds may include additional substitution that occurs after the initial ether linkage, such as aryl, heteroaryl, heterocyclyl, amido, sulfonamido, urea, and the like. An additional set of compounds provided by the invention contain a thioether linkage at the 1-position; these thioether compounds may also have additional substitution after the initial thioether linkage, including alkyl, aryl, heteroaryl, and heterocyclyl.